Eylea 40 mg/ml solucion inyectable en jeringa precargada

Patient Information: Adult

Eylea 40 mg/ml Injectable Solution in Pre-filled Syringe

aflibercept

ADULTS

For information for the caregivers of premature babies, see the end of section 6

Read this entire leaflet carefully before you receive this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, ask your doctor, even if they are not listed in this leaflet. See section 4.

Eylea is a solution that is injected into the eye to treat certain eye diseases in adult patients, known as:

• age-related macular degeneration with neovascularization (exudative) commonly known as exudative age-related macular degeneration (AMD)
• vision loss due to macular edema caused by blockage of the retinal veins (central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO))
• vision loss due to diabetic macular edema (DME)
• vision loss due to choroidal neovascularization in myopic eyes (CNVM)

Aflibercept, the active ingredient in Eylea, blocks the activity of a group of factors called vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF).

In patients with exudative AMD and CNVM, when these factors are present in excess, they influence the formation of abnormal new blood vessels in the eye. These new blood vessels can cause leakage of blood components into the eye, resulting in damage to the ocular tissues responsible for vision.

In patients with CRVO, a blockage of the main vein that transports blood from the retina occurs. As a result, VEGF levels increase, causing fluid leakage in the retina and subsequent macular swelling (the part of the retina responsible for fine vision), known as macular edema.

When the macula becomes filled with fluid, central vision becomes blurry.

In patients with BRVO, a blockage of one or more branches of the main blood vessel that transports blood from the retina occurs. As a result, VEGF levels increase, causing fluid leakage in the retina and subsequent macular swelling.

Diabetic macular edema is a swelling of the retina that occurs in patients with diabetes due to leakage of fluid from the blood vessels of the macula. The macula is the part of the retina responsible for fine vision. When the macula becomes swollen with fluid, central vision becomes blurry.

Eylea has been shown to stop the growth of abnormal new blood vessels in the eye that often bleed or leak fluid. Eylea can help stabilize and, in many cases, improve vision loss caused by exudative AMD, CRVO, BRVO, DME, and CNVM.

You should not be given Eylea

• if you are allergic to aflibercept or any of the other components of this medication (listed in section 6)
• if you have an active infection or suspect you may have an infection in the eye or around it (ocular or periocular infection)
• if you have a severe inflammation of the eye (indicated by pain or redness)

Warnings and precautions

Consult your doctor before Eylea is administered to you:

• If you have glaucoma.
• If you have a history of flashes of light or floating particles in your vision or if your vision suddenly worsens and the number and size of floating particles increase.
• If you have had surgery or are scheduled for surgery in your eye within the past four weeks or in the four weeks following.
• If you have a severe form of diabetic retinopathy or macular edema (DR or ME), treatment with Eylea is not recommended.

Additionally, you should be aware that:

• The safety and efficacy of Eylea when administered in both eyes at the same time have not been studied and may increase the risk of adverse effects.
• Eylea injections may cause an increase in intraocular pressure in some patients within 60 minutes following the injection. Your doctor will monitor you after each injection.
• If you develop an infection or inflammation in the inner part of the eye (endophthalmitis) or other complications, you may notice pain or increased discomfort in the eye, worsening of eye redness, blurred or decreased vision, and increased sensitivity to light. Any symptom that appears should be diagnosed and treated as soon as possible.
• Your doctor will check if you have other risk factors that may increase the likelihood of retinal detachment or posterior vitreous detachment (PVD) and, if so, Eylea will be administered with caution.
• Eylea should not be used during pregnancy, unless the potential benefit outweighs the potential risk to the fetus.
• Women of childbearing age should use effective contraceptive methods during treatment and for at least three months after the last Eylea injection.

The systemic use of VEGF inhibitors, substances similar to those contained in Eylea, is potentially related to the risk of arterial thromboembolic events, which may lead to myocardial infarction or stroke. There is a theoretical risk of these events occurring after Eylea injection in the eye. Data on the safety of treating patients with DR, ME, or NVC myopia who have had a stroke, transient ischemic attack (TIA), or myocardial infarction in the past six months are limited. If any of these cases apply to you, Eylea will be administered with caution.

Experience is limited in the treatment of:

• Patients with ME due to type 1 diabetes.
• Diabetic patients with very high mean blood sugar levels (Hemoglobin A1c greater than 12%).
• Diabetic patients with diabetic retinopathy, a condition known as proliferative diabetic retinopathy.

There is no experience in the treatment of:

• Patients with acute infections.
• Patients with other eye conditions such as retinal detachment or macular hole.
• Diabetic patients with uncontrolled hypertension.
• Non-Asian patients with NVC myopia.
• Patients who have been previously treated for NVC myopia.
• Patients with extrafoveal lesions due to NVC myopia.

If any of the above applies to you, your doctor will take this lack of information into account when treating you with Eylea.

Children and adolescents

Eylea has not been studied in children and adolescents under 18 years old for indications other than retinopathy of prematurity (ROP).

Other medications and Eylea

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Pregnancy and breastfeeding

• Women of childbearing age should use effective contraceptive methods during treatment and for at least three months after the last Eylea injection.
• There is no experience with the use of Eylea in pregnant women. Eylea should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant or plan to become pregnant, discuss this with your doctor before treatment with Eylea.
• Small amounts of Eylea may pass into breast milk. The effects on newborns/breastfed infants are unknown. Eylea is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with Eylea.

Driving and operating machinery

After Eylea injection, you may experience some transient visual disturbances. Do not drive or operate machinery while these disturbances last.

Eylea contains

• less than 1 mmol of sodium (23 mg) per dose; essentially "sodium-free".
• 0.015 mg of polisorbate 20 in each 0.05 ml dose equivalent to 0.3 mg/ml. Polisorbates can cause allergic reactions. Inform your doctor if you have any known allergies.

Eylea will be administered by an experienced doctor in the administration of eye injections, in sterile conditions (clean and aseptic).

The recommended dose is 2 mg of aflibercept (0.05 ml).

Eylea is administered as an injection into the interior of the eye (intravitreal injection).

Before the injection, your doctor will use an antiseptic eye wash to carefully clean your eye to prevent infection. Your doctor will also administer a local anesthetic to reduce or prevent any pain you may feel with the injection.

Diabetic Macular Edema (DME)

Patients with DME will be treated with a monthly injection for the first three doses, followed by another injection after two more months.

Your doctor will then decide if the treatment interval between injections can be maintained every two months or gradually extended in intervals of 2 or 4 weeks if your disease has stabilized. If your disease worsens, the interval between injections may be shortened.

You do not need to visit your doctor between injections, unless your doctor considers it necessary or you experience any problems.

Secondary Macular Edema due to Branch or Central Retinal Vein Occlusion (RVO)

Your doctor will determine the most suitable treatment program for you. Your treatment will begin with a series of Eylea injections administered once a month.

The interval between two injections should not be less than one month.

Your doctor may decide to discontinue treatment with Eylea if you do not benefit from continued treatment.

Treatment will continue with a monthly injection until your disease stabilizes. You may need three or more monthly injections.

Your doctor will monitor your response to treatment and may continue treatment, gradually increasing the interval between injections to stabilize your disease. If your disease worsens with a longer treatment interval, your doctor will reduce the interval between injections.

Based on your response to treatment, your doctor will decide on the follow-up and treatment program.

Diabetic Macular Edema (DME)

Patients with DME will be treated with a monthly injection for the first five consecutive doses, and then a bi-monthly injection.

The treatment interval may be maintained every two months or adjusted according to your disease based on your doctor's examination. Your doctor will decide on the follow-up visit program.

Your doctor may decide to discontinue treatment with Eylea if they find that you do not benefit from continued treatment.

Myopic Choroidal Neovascularization (CNV)

Patients with myopic CNV will be treated with a single injection. You will only receive more injections if your doctor's examinations reveal that your disease has not improved.

The interval between two injections should not be less than one month.

If your disease disappears and then returns, your doctor may restart treatment.

Your doctor will decide on the follow-up review program.

Instructions for use are provided in detail at the end of this prospectus in “How to prepare and administer Eylea to adults”.

If you are not administered a dose of Eylea

Request a new appointment for your doctor to examine and administer the injection.

Discontinuation of Eylea treatment

Consult your doctor before discontinuing treatment.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

They may potentially causeallergic reactions(hypersensitivity).These can be serious andrequire immediate contact with your doctor.

With the administration of Eylea, some side effects that affect the eyes may occur due to the injection procedure. Some may beserious, includingblindness,aserious infection or inflammation in the interior of the eye(endophthalmitis),retinal detachment, tear, or hemorrhage of the light-sensitive layer in the back of the eye(retinal detachment or tear),clouding of the lens(cataract),bleeding in the eye(vitreous hemorrhage),retinal detachment of the substance similar to a gel that is located in the interior of the eye in contact with the retina(vitreous detachment) andincreased pressure in the interior of the eye(see section 2). These serious eye side effects occurred in less than 1 in 1,900 injections during clinical trials.

If you notice a sudden decrease in vision or an increase in pain and redness in the eye after the injection,consult your doctor immediately.

List of reported side effects

The following is a list of reported side effects that may be related to the injection procedure or the medicine. Do not be alarmed, as you may not experience any of them. Always consult your doctor about any suspected side effect.

Very common side effects(may affect more than 1 in 10 people):

• vision loss
• retinal hemorrhage
• bleeding in the outer layers of the eye due to small blood vessel rupture
• eye pain

Common side effects(may affect up to 1 in 10 people):

• retinal detachment or tear, which may cause flashes of light with floaters that may progress to vision loss (retinal pigment epithelium tear or detachment, retinal tear or detachment)
• • *Side effects associated with exudative DMAE; observed only in patients with exudative DMAE.

• retinal degeneration (causing vision disturbances)
• vitreous hemorrhage
• certain forms of cataract
• corneal damage
• increased intraocular pressure
• floaters in the vision
• vitreous detachment, which results in flashes of light with floaters
• feeling of something in the eye
• excessive tear production
• swelling of the eyelid
• bleeding at the injection site
• eye redness

Uncommon side effects(may affect up to 1 in 100 people):

• allergic reactions (hypersensitivity)**
• • **Allergic reactions reported as rash, itching (pruritus), hives (urticaria), and some cases of severe allergic reactions (anaphylactic/anaphylactoid).
• serious inflammation or infection inside the eye (endophthalmitis)
• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, cells floating in the anterior chamber)
• abnormal sensation in the eye
• irritation of the eyelid
• swelling of the cornea

Rare side effects(may affect up to 1 in 1,000 people)

• blindness
• cataract due to injury

• inflammation of the vitreous with pus in the eye

Unknown frequency(cannot be estimated from available data):

• inflammation of the white part of the eye associated with redness and pain (scleritis)

In clinical trials, an increase in the incidence of small blood vessel rupture in the outer layers of the eye (conjunctival hemorrhage) was observed in patients with exudative DMAE receiving anticoagulant treatment. This increase in incidence was comparable in patients treated with ranibizumab and Eylea.

The use of VEGF inhibitors by systemic route, substances similar to those contained in Eylea, is potentially related to the risk of blood clots that block blood vessels (arterial thromboembolic events) that may cause a heart attack or embolism. There is a theoretical risk that this type of event may occur after Eylea injection in the eye.

Like all therapeutic proteins, there is a possibility of an immune reaction (antibody formation) with Eylea.

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and on the label after “CAD/EXP”. The expiration date is the last day of the month indicated.
• Store in refrigerator (between2 °Cand8 °C). Do not freeze.
• The unopened blister pack can be stored outside the refrigerator below25 °Cfor a maximum of 24 hours.
• Store in the original packaging to protect it from light.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Eylea

• The active ingredient is: aflibercept. A pre-filled syringe contains a withdrawable volume of at least 0.09 ml, equivalent to at least 3.6 mg of aflibercept. A pre-filled syringe provides a dose of 2 mg of aflibercept in 0.05 ml.
• The other components are: polisorbate 20 (E 432), dihydrogen phosphate monohydrate (for pH adjustment), hydrogen phosphate heptahydrate (for pH adjustment), sodium chloride, sucrose, water for injection.

See “Eylea contains” in section 2 for more information.

Appearance of the product and contents of the pack

Eylea is a solution for injection (injectable) in a pre-filled syringe. The solution is colourless to pale yellow.

Pack containing 1 pre-filled syringe.

Marketing authorisation holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Müllerstraße 178

13353 Berlin

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:https://www.ema.europa.eu.

If you wish to have information on this medicinal product, scan here to access the websitehttps://www.pi.bayer.com/eylea1.

A QR code with the link to the leaflet is included.

<------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

How to prepare and administer Eylea to premature babies

The pre-filled syringe must be usedfor the treatment of a single eye. The extraction of multiple doses from a pre-filled syringe may increase the risk of contamination and subsequent infection.

Do not open the sterile pre-filled syringe outside the clean room. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

The pre-filled syringe contains more volume than the recommended dose of 0.4 mg of aflibercept (equivalent to 0.01 ml). For the treatment of premature babies, the pediatric dosing device PICLEO must be used in combination with the pre-filled syringe to administer a single dose of 0.4 mg of aflibercept (equivalent to 0.01 ml). See the following section “Instructions for use of the pre-filled syringe”.

Before administration, the solution must be visually inspected to detect the presence of particles and/or a change in color or any change in physical appearance. If you observe any of them, do not use the medication.

The unopened blister pack can be stored outside the refrigerator below 25°C for a maximum of 24 hours. After opening the blister pack, proceed under aseptic conditions.

For intravitreal injection, a 30 G x ½ inch (1.27 cm) injection needle must be used.

Instructions for use of the pre-filled syringe:

To prepare the pre-filled syringe for administration to premature babies, follow steps 1 and 2 below and then follow the instructions for use included in the packaging of the pediatric dosing device PICLEO.

1. When ready to administer Eylea, open the box and remove the sterile blister pack. Carefully peel off the backing of the blister pack, ensuring the sterility of its contents. Keep the syringe in the sterile tray until ready for assembly.
2. Using aseptic technique, remove the syringe from the sterile blister pack.